Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization.
Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization.
复制标题
破骨细胞可用于造血干细胞维持和动员。
DOI：
10.1084/jem.20101890
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发表时间：
2011-10-24
期刊：
影响因子：
--
通讯作者：
Miyamoto T
中科院分区：
文献类型：
--
作者：
Miyamoto K;Yoshida S;Kawasumi M;Hashimoto K;Kimura T;Sato Y;Kobayashi T;Miyauchi Y;Hoshi H;Iwasaki R;Miyamoto H;Hao W;Morioka H;Chiba K;Kobayashi T;Yasuda H;Penninger JM;Toyama Y;Suda T;Miyamoto T
造血干细胞的动员不需要破骨细胞，甚至可能有抑制作用。造血干细胞(HSCs)维持在特定的骨髓(BM)壁龛中，由破骨细胞形成的空腔中。破骨细胞缺陷的小鼠是有骨角化的，并表现出闭合的骨髓腔。破骨细胞活性与造血活性呈负相关；然而，破骨细胞和骨髓腔如何潜在地调节造血尚不清楚。为了研究这个问题，我们评估了三种骨化小鼠模型的造血活性：OP/OP、c-Fos缺陷和RANKL(核因子kappa B配体受体激活物)缺陷小鼠。我们发现，尽管这些动物中没有破骨细胞，因此也没有骨髓腔，但注射粒细胞集落刺激因子后，所有三个品系的造血干细胞和祖细胞(HSPC)动员能力都与野生型小鼠相当，甚至更高。相比之下，骨保护素缺乏的小鼠破骨细胞数量增加，HSPC动员减少。据报道，骨髓缺乏的患者和小鼠在髓外空间，如脾，保持了造血；然而，切除脾的OP/OP小鼠并没有表现出HSPC动员的减少。有趣的是，我们在OP/OP小鼠的骨质中检测到了HSC群体，而药物消融野生型小鼠的破骨细胞并没有抑制甚至增加HSPC的动员。这些结果表明，破骨细胞在HSC动员中是必不可少的，可能在造血系统中起负调控作用。
The mobilization of hematopoietic stem cells does not require osteoclasts, which may even have an inhibitory effect. Hematopoietic stem cells (HSCs) are maintained in a specific bone marrow (BM) niche in cavities formed by osteoclasts. Osteoclast-deficient mice are osteopetrotic and exhibit closed BM cavities. Osteoclast activity is inversely correlated with hematopoietic activity; however, how osteoclasts and the BM cavity potentially regulate hematopoiesis is not well understood. To investigate this question, we evaluated hematopoietic activity in three osteopetrotic mouse models: op/op, c-Fos-deficient, and RANKL (receptor activator of nuclear factor kappa B ligand)-deficient mice. We show that, although osteoclasts and, by consequence, BM cavities are absent in these animals, hematopoietic stem and progenitor cell (HSPC) mobilization after granulocyte colony-stimulating factor injection was comparable or even higher in all three lines compared with wild-type mice. In contrast, osteoprotegerin-deficient mice, which have increased numbers of osteoclasts, showed reduced HSPC mobilization. BM-deficient patients and mice reportedly maintain hematopoiesis in extramedullary spaces, such as spleen; however, splenectomized op/op mice did not show reduced HSPC mobilization. Interestingly, we detected an HSC population in osteopetrotic bone of op/op mice, and pharmacological ablation of osteoclasts in wild-type mice did not inhibit, and even increased, HSPC mobilization. These results suggest that osteoclasts are dispensable for HSC mobilization and may function as negative regulators in the hematopoietic system.
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